The Activation Mechanism of the Insulin Receptor: A Structural Perspective.

The insulin receptor (IR) is a type II receptor tyrosine kinase that plays essential roles in metabolism, growth, and proliferation. Dysregulation of IR signaling is linked to many human diseases, such as diabetes and cancers. The resolution revolution in cryo-electron microscopy has led to the determination of several structures of IR with different numbers of bound insulin molecules in recent years, which have tremendously improved our understanding of how IR is activated by insulin. Here, we review the insulin-induced activation mechanism of IR, including (a) the detailed binding modes and functions of insulin at site 1 and site 2 and (b) the insulin-induced structural transitions that are required for IR activation. We highlight several other key aspects of the activation and regulation of IR signaling and discuss the remaining gaps in our understanding of the IR activation mechanism and potential avenues of future research.

Mitotic Checkpoint Regulators Control Insulin Signaling and Metabolic Homeostasis.

Insulin signaling regulates many facets of animal physiology. Its dysregulation causes diabetes and other metabolic disorders. The spindle checkpoint proteins MAD2 and BUBR1 prevent precocious chromosome segregation and suppress aneuploidy. The MAD2 inhibitory protein p31(comet) promotes checkpoint inactivation and timely chromosome segregation. Here, we show that whole-body p31(comet) knockout mice die soon after birth and have reduced hepatic glycogen. Liver-specific ablation of p31(comet) causes insulin resistance, hyperinsulinemia, glucose intolerance, and hyperglycemia and diminishes the plasma membrane localization of the insulin receptor (IR) in hepatocytes. MAD2 directly binds to IR and facilitates BUBR1-dependent recruitment of the clathrin adaptor AP2 to IR. p31(comet) blocks the MAD2-BUBR1 interaction and prevents spontaneous clathrin-mediated IR endocytosis. BUBR1 deficiency enhances insulin sensitivity in mice. BUBR1 depletion in hepatocytes or the expression of MAD2-binding-deficient IR suppresses the metabolic phenotypes of p31(comet) ablation. Our findings establish a major IR regulatory mechanism and link guardians of chromosome stability to nutrient metabolism.

Author Correction: CPS1 maintains pyrimidine pools and DNA synthesis in KRAS/LKB1-mutant lung cancer cells.

Further analysis has revealed that the signal reported in Extended Data Fig. 1c of this Letter is attributed to phosphorylethanolamine, not carbamoyl phosphate. A newly developed derivatization method revealed that the level of carbamoyl phosphate in these NSCLC extracts is below the detection threshold of approximately 10 nanomoles. These findings do not alter the overall conclusions of the Letter; see associated Amendment for full details. The Letter has not been corrected online.

CPS1 maintains pyrimidine pools and DNA synthesis in KRAS/LKB1-mutant lung cancer cells.

Metabolic reprogramming by oncogenic signals promotes cancer initiation and progression. The oncogene KRAS and tumour suppressor STK11, which encodes the kinase LKB1, regulate metabolism and are frequently mutated in non-small-cell lung cancer (NSCLC). Concurrent occurrence of oncogenic KRAS and loss of LKB1 (KL) in cells specifies aggressive oncological behaviour. Here we show that human KL cells and tumours share metabolomic signatures of perturbed nitrogen handling. KL cells express the urea cycle enzyme carbamoyl phosphate synthetase-1 (CPS1), which produces carbamoyl phosphate in the mitochondria from ammonia and bicarbonate, initiating nitrogen disposal. Transcription of CPS1 is suppressed by LKB1 through AMPK, and CPS1 expression correlates inversely with LKB1 in human NSCLC. Silencing CPS1 in KL cells induces cell death and reduces tumour growth. Notably, cell death results from pyrimidine depletion rather than ammonia toxicity, as CPS1 enables an unconventional pathway of nitrogen flow from ammonia into pyrimidines. CPS1 loss reduces the pyrimidine to purine ratio, compromises S-phase progression and induces DNA-polymerase stalling and DNA damage. Exogenous pyrimidines reverse DNA damage and rescue growth. The data indicate that the KL oncological genotype imposes a metabolic vulnerability related to a dependence on a cross-compartmental pathway of pyrimidine metabolism in an aggressive subset of NSCLC.

Association of Homelessness with Hospital Readmissions-an Analysis of Three Large States.

BACKGROUND: Individuals experiencing homelessness have higher hospitalization and mortality rates compared with the housed. Whether they also experience higher readmission rates, and if readmissions vary by region or cause of hospitalization is unknown. OBJECTIVE: Evaluate the association of homelessness with readmission rates across multiple US states. DESIGN: Retrospective analysis of administrative claims PATIENTS: All inpatient hospitalizations in Florida, Massachusetts, and New York from January 2010 to October 2015 MAIN MEASURES: Thirty- and 90-day readmission rates KEY RESULTS: Out of a total of 23,103,125 index hospitalizations, 515,737 were for patients who were identified as homeless at the time of discharge. After adjusting for cause of index hospitalization, state, demographics, and clinical comorbidities, 30-day and 90-day readmission rates were higher for index hospitalizations in the homeless compared with those in the housed group. The difference in 30-day readmission rates between homeless and housed groups was the largest in Florida (30.4% vs. 19.3%; p < 0.001), followed by Massachusetts (23.5% vs. 15.2%; p < 0.001) and New York (15.7% vs. 13.4%; p < 0.001) (combined 17.3% vs. 14.0%; p < 0.001). Among the most common causes of hospitalization, 30-day readmission rates were 4.1 percentage points higher for the homeless group for mental illness, 4.9 percentage points higher for diseases of the circulatory system, and 2.4 percentage points higher for diseases of the digestive system. CONCLUSIONS: After adjusting for demographic and clinical characteristics, homelessness is associated with significantly higher 30- and 90-day readmission rates, with a significant variation across the three states. Interventions to reduce the burden of readmissions among individuals experiencing homelessness are urgently needed. Differences across states point to the potential of certain public policies to impact health outcomes for individuals experiencing homelessness.

Frailty and related outcomes in patients undergoing transcatheter valve therapies in a nationwide cohort.

AIMS: We sought to identify the prevalence and related outcomes of frail individuals undergoing transcatheter mitral valve repair and transcatheter aortic valve replacement (TAVR). METHODS AND RESULTS: Patients aged 65 and older were included in the study if they had at least one procedural code for transcatheter mitral valve repair or TAVR between 1 January 2016 and 31 December 2016 in the Centers for Medicare and Medicaid Services Medicare Provider and Review database. The Hospital Frailty Risk Score, an International Classification of Diseases, Tenth Revision (ICD-10) claims-based score, was used to identify frailty and the primary outcome was all-cause 1-year mortality. A total of 3746 (11.6%) patients underwent transcatheter mitral valve repair and 28 531 (88.4%) underwent TAVR. In the transcatheter mitral valve repair and TAVR populations, respectively, there were 1903 (50.8%) and 14 938 (52.4%) patients defined as low risk for frailty (score <5), 1476 (39.4%) and 11 268 (39.5%) defined as intermediate risk (score 5-15), and 367 (9.8%) and 2325 (8.1%) defined as high risk (score >15). One-year mortality was 12.8% in low-risk patients, 29.7% in intermediate-risk patients, and 40.9% in high-risk patients undergoing transcatheter mitral valve repair (log rank P < 0.001). In patients undergoing TAVR, 1-year mortality rates were 7.6% in low-risk patients, 17.6% in intermediate-risk patients, and 30.1% in high-risk patients (log rank P < 0.001). CONCLUSIONS: This study successfully identified individuals at greater risk of short- and long-term mortality after undergoing transcatheter valve therapies in an elderly population in the USA using the ICD-10 claims-based Hospital Frailty Risk Score.

Trends, Causes, and Outcomes of Hospitalizations for Homeless Individuals: A Retrospective Cohort Study.

OBJECTIVES: In the United States, an estimated 553,000 people are homeless on any given night. Few data provide large-scale, contemporary insight with regard to recent patterns of acute illness in this vulnerable population. We evaluated patterns, causes, and outcomes of acute hospitalization among homeless persons compared with a demographics-standardized and risk-standardized nonhomeless cohort. METHODS: Retrospective study comparing 185,292 hospitalizations for homeless individuals and 32,322,569 hospitalizations for demographics-standardized nonhomeless individuals between 2007 and 2013 in Massachusetts, Florida, and California. Annual hospitalization rates for homeless persons were calculated and causes of hospitalization were compared with a demographics-standardized nonhomeless cohort. Logistic and linear regression models were used to estimate risk-standardized outcomes. RESULTS: From 2007 to 2013, hospitalizations for the homeless increased in Massachusetts (294 to 420 hospitalizations per 1000 homeless residents), Florida (161 to 240/1000), and California (133 to 164/1000). Homeless patients were on average 46 years of age, often male (76.1%), white (62%), and either uninsured (41.9%) or insured by Medicaid (31.7%). Hospitalizations for homeless persons, compared with demographics-standardized nonhomeless, were more frequently for mental illness and substance use disorder (52% vs. 18%, P<0.001). Homeless compared with risk-standardized nonhomeless individuals had lower in-hospital mortality rates (0.9% vs. 1.2%, P<0.001), longer mean length of stay (6.5 vs. 5.9 d, P<0.001), and lower mean costs per day ($1 535 vs. $1 834, P<0.001). CONCLUSIONS: Hospitalizations among homeless persons are rising. Despite greater policy and public health focus over the last few decades, mental illness and substance use remain primary drivers of acute hospitalization among homeless adults. Policy efforts should address barriers to the use of ambulatory care services, and behavioral health services in particular, to help reduce acute care use and improve the long-term health of homeless individuals.

Long-term Prognosis of Acute-on-Chronic Liver Failure Survivors.

GOALS: We aimed to investigate significant factors influencing the long-term prognosis of patients who survived acute-on-chronic liver failure (ACLF). BACKGROUND: The mortality of ACLF is predominantly affected by the organ failure severity. However, long-term outcomes of patients who survive ACLF are not known. STUDY: A cohort of 1084 cirrhotic patients who survived for more than 3 months following acute deterioration of liver function was prospectively followed. ACLF was defined by the European Association for the Study of the Liver Chronic Liver Failure Consortium definition. RESULTS: The mean follow-up duration was 19.4±9.9 months. In the subgroup of patients without previous acute decompensation (AD), ACLF occurrence did not affect long-term outcomes. However, in patients with previous AD, ACLF negatively affected long-term transplant-free survival even after overcoming ACLF (hazard ratio, 2.00, P=0.012). Previous AD was the significant predictive factor of long-term mortality and was independent of the Model for End-stage Liver Disease score in these ACLF-surviving patients. Organ failure severity did not affect transplant-free survival in patients who survived an ACLF episode. CONCLUSIONS: A prior history of AD is the most important factor affecting long-term outcomes following an ACLF episode regardless of Model for End-stage Liver Disease score. Prevention of a first AD episode may improve the long-term transplant-free survival of liver cirrhosis patients.

Factors influencing colonoscopy behaviour among Koreans with a positive faecal occult blood tests.

OBJECTIVE: Colonoscopy is important for colorectal cancer (CRC) screening in individuals with a positive faecal occult blood test (FOBT). The purpose of the present study was to identify factors affecting the colonoscopy screening behaviour of FOBT-positive individuals, based on the health belief model (HBM). METHODS: This study involved a cross-sectional survey of 213 individuals aged 50 years or older who underwent CRC screening at a general hospital in Seoul, Korea, as part of the Korean National Cancer Screening Programme and who tested positive on FOBT. The questionnaire was created based on HBM instruments. The collected data were analysed using descriptive statistics, and factors associated with adherence to colonoscopy were examined using logistic regression analysis. RESULTS: Of the FOBT-positive individuals, 44.1% adhered to colonoscopy. Three of the six evaluated HBM-driven factors (perceived seriousness, perceived barriers and health motivation) significantly differed between colonoscopy-adherent and non-adherent subjects. Perceived seriousness and perceived barriers were the most important factors influencing colonoscopy screening behaviour. CONCLUSION: For early detection and prevention of CRC, colonoscopy screening behaviour should improve among FOBT-positive individuals. To this aim, education on the graveness of CRC should be provided, and barriers to CRC screening should be addressed.

The New Cutoff Value of the Hepatic Venous Pressure Gradient on Predicting Long-Term Survival in Cirrhotic Patients.

BACKGROUND: This study aimed to determine the prognostic role of the categorized hemodynamic stage (HS) based on the hepatic venous pressure gradient (HVPG) in patients with portal hypertension. METHODS: Of 1,025 cirrhotic patients who underwent HVPG measurement, data on 572 non-critically-ill patients were collected retrospectively between 2008 and 2013. The following two HS categorizations were used: HS-1 (6-9, 10-12, 13-16, 17-20, and > 20 mmHg; designated as groups 1-5, respectively) and HS-2 (6-12, 13-20, and > 20 mmHg). Clinical characteristics, mortality rates, and prognostic predictors were analyzed according to the categorized HS. RESULTS: During the mean follow-up period of 25 months, 86 (15.0%) patients died. The numbers of deaths in HS-1 groups were 7 (6.3%), 7 (6.9%), 30 (18.0%), 20 (15.6%), and 22 (34.4%), respectively (P < 0.001). However, the traditional HVPG cutoffs of 10 and 16 mmHg did not improve the discrimination of mortality. In contrast, the mortality rates did differ significantly between the three HS-2 groups (P < 0.05). In the multivariate analysis, all models revealed that HS-2 was a common prognostic factor in predicting mortality. The mortality rates increased significantly according to HS-2 in patients with hypoalbuminemia (HVPG, 13-20 mmHg; hazard ratio [HR], 2.54 and HVPG > 20 mmHg; HR, 5.45) and intermediate model for end-stage liver disease (MELD) score (HVPG, 13-20 mmHg; HR, 3.86 and HVPG > 20 mmHg; HR, 8.77; P < 0.05). CONCLUSION: Categorizing HVPG values according to HS-2 is a useful prognostic modality in patients with portal hypertension and can play an independent role in predicting the prognosis in patients with hypoalbuminemia and an intermediate MELD score.

Diabetes Mellitus is Associated With Mortality in Acute Pancreatitis.

BACKGROUND AND AIM: Predicting severe pancreatitis is important for early aggressive management of patients with acute pancreatitis (AP). Despite the established role of diabetes mellitus (DM) in the risk of AP, the impact of DM on the clinical outcome in AP has not been fully elucidated. The objective of this study was to assess the risk of mortality and severity in AP among patients with type-2 DM. METHODS: Patients diagnosed with first attacks of AP were enrolled from January 2013 to June 2015. RESULTS: A total of 201 patients (63.2% male, mean age, 59.4 y) with AP were included. Etiologies included gallstones (51.2%), alcohol (37.3%), hypertriglyceridemia (2%), and idiopathic causes (9.5%). There were 54 AP patients (26.9%) with type-2 DM. Severity indices in AP, such as Atlanta Classification (severe), Ranson score, and Bedside Index of Severity in Acute Pancreatitis, were higher in subjects with DM than those without DM. Prevalence of intensive care unit admission and mortality were higher in AP patients with DM compared with those without DM. The association between DM and increased risk of mortality in AP remained statistically significant even after adjustments for confounding factors and Atlanta Classification (odds ratio, 7.76, 95% confidence interval, 1.26-47.63, P=0.027). CONCLUSIONS: Type-2 DM was associated with severity and increased mortality in patients with AP. Our findings provide evidence of the potential role of DM in the pathogenesis and management of severe AP.

Waist-to-height ratio index for predicting incidences of hypertension: the ARIRANG study.

BACKGROUND: Several anthropometric indices such as body mass index (BMI) and waist circumference (WC) have been examined as indicators of cardiovascular diseases, in both adults and children. However, the waist-to-height ratio (WHtR) is considered a better predictor for the detection of cardiovascular risk factors, than BMI. We investigated the association between the WHtR and incident hypertension. METHODS: A total of 1718 participants, aged 39-72 years, were recruited in this longitudinal study. Participants were divided into 2 groups according to the development of hypertension during 2005-2008 (baseline) and 2008-2011 (follow-up). Logistic regression models were used to evaluate the WHtR as a significant predictor of hypertension. RESULTS: During the 2.8 years of follow-up, 185 new cases of hypertension (10.8%) were diagnosed, with an incidence rate of approximately 4% per year. The WHtR was significantly higher in the participants who had developed hypertension than in those who had not (0.54 ± 0.05 vs. 0.51 ± 0.05, p < 0.001). After adjusting for age, sex, smoking status, alcohol intake, regular exercise status, total cholesterol, and systolic blood pressure, at the baseline, the logistic regression analysis indicated that the participants with the highest quartile of the WHtR (WHtR≥0.54) were 4.51 times more likely to have hypertension than those with the lowest quartile (odds ratio 4.51; 95% confidence interval 2.41-8.43; p < .0001). The area under the curve for the WHtR, in identifying hypertension risk, was significantly greater than that for the BMI (p = 0.0233). CONCLUSION: A positive association between WHtR and the incidence of hypertension was observed in Korean adults. The findings of the present community-based prospective study suggest that the WHtR may be a better predictor of incident hypertension.

Understanding work enjoyment among older workers: The significance of flexible work options and age discrimination in the workplace.

Although the number of older workers in the U.S. is increasing, there is a gap in knowledge on whether or not they actually enjoy working. This study, based on a conceptual framework focusing on job resources and demands, explored likely workplace determinants of work enjoyment among older workers aged 50 or over. Using the 2012 wave of the Health and Retirement Study, a partial proportional odds model was used to detect determinants of work enjoyment. Results showed that higher levels of work enjoyment were significantly and negatively associated with the level of perceived retirement pressure and promotion preference for younger workers, and positively associated with moving to less demanding positions. Self-employment showed a noticeable enhancement of work enjoyment. This study highlights the significance of flexible work options and age discrimination in the workplace in understanding work enjoyment later in life.

Prognostic Significance of Hemodynamic and Clinical Stages in the Prediction of Hepatocellular Carcinoma.

BACKGROUND & GOALS: Early identification of hepatocellular carcinoma (HCC) is associated with improved survival for patients with chronic liver disease (CLD). We evaluated the prognostic significance of hemodynamic stage (HS) and clinical stage (CS) in predicting HCC in CLD patients. METHODS: Between January 2006 and May 2014, 801 patients with CLD who underwent hepatic venous pressure gradient (HVPG) measurement were prospectively enrolled. HS was classified by HVPG (mm Hg) as follows: HS-1 (HVPG≤6), HS-2 (612 mm Hg (P=0.033, OR=2.17), CS>2 (P=0.039, OR=2.36), and alpha-fetoprotein (AFP; P=0.017, OR=1.01) were significant predictors of HCC development in all patients. For patients with cirrhosis, ascites aggravation (OR=2.51), HVPG >12 mm Hg (OR=2.46), and CS >2 (OR=2.62) were correlated with HCC development. Areas under receiver operating characteristic curves of the prediction-model, CS, HVPG score, and AFP were 0.797, 0.707, 0.701, and 0.653, respectively. CONCLUSIONS: HCC development correlates with advancing liver fibrosis or disease as measured by HS and CS. In addition, ascites aggravation and elevated AFP appears to be associated with increased incidence of HCC.

Comparison of push-out bond strength of fiber-reinforced composite resin posts according to cement thickness.

STATEMENT OF PROBLEM: Post space size and cement thickness can differ because of variations in root canal morphology, such as an oval shape, and because the entire canal space cannot be included in the post space preparation. As a result, increased cement thickness around the post may affect the bond strength between the post and the dentin. PURPOSE: The purpose of this in vitro study was to evaluate the push-out bond strength of fiber-reinforced composite resin posts to root dentin with cement layers of varying thickness. MATERIAL AND METHODS: Thirty human premolars were endodontically treated and restored with fiber-reinforced composite resin posts. Post space was prepared using a drill with a 1.5-mm diameter and diameters of 1.25 mm (small [S] group), 1.375 mm (medium [M] group), and 1.5 mm (large [L] group) were cemented. The specimens were sectioned horizontally into 1-mm-thick slices, and the push-out bond strengths of the apical and coronal fragments were evaluated. Bond strength was compared using analysis of variance and 2-sample t tests (α=.05). RESULTS: No significant differences were found in the debonding force and push-out bond strength among fiber-reinforced composite posts of different sizes (P>.05). The mean debonding force and standard deviation of the posts were 25.05 ±9.52 N for the S group, 28.17 ±11.38 N for the M group, and 33.78 ±12.47 N for the L group. The corresponding push-out bond strength values were 3.11 ±1.54 MPa, 3.39 ±1.4 MPa, and 4.15 ±1.75 MPa. The differences in debonding force between the apical (26.43 ±10.72 N) and coronal (31.57 ±12.03 N) areas were not significant (P>.05). However, the differences in push-out bond strength between the apical (4.27 ±1.73 MPa) and coronal areas (2.83 ±1.08 MPa) were significant (P<.05). CONCLUSIONS: The widening of post spaces and, consequently, the increased cement thickness do not significantly affect the bond strength of fiber-reinforced composite resin posts to root dentin.

Switching from prasugrel to clopidogrel based on Cytochrome P450 2C19 genotyping in East Asian patients stabilized after acute myocardial infarction.

To evaluate the pharmacodynamic efficacy of de-escalating P2Y12 inhibition from prasugrel to clopidogrel based on cytochrome P450 (CYP) 2C19 genotyping, we genotyped 50 Korean patients with AMI who underwent percutaneous coronary intervention (PCI) for CYP2C19 *2,*3, or *17 using real-time PCR. They were discharged on prasugrel 10 mg daily. A control group of 48 AMI patients who underwent PCI and were discharged on clopidogrel but did not undergo genotyping was identified retrospectively. Based on genotyping results available at 3 weeks, 12 patients found to have 2 copies of either CYP2C19 *2 or *3 loss of function alleles continued prasugrel while the remaining 38 patients switched to clopidogrel 75 mg daily. The rate of patients within the therapeutic window (TW) of on-treatment platelet reactivity (OPR), 85

A Randomized Controlled Trial of Compression Rates during Cardiopulmonary Resuscitation.

UNLABELLED: The objective of this study was to compare the efficacy of cardiopulmonary resuscitation (CPR) with 120 compressions per minute (CPM) to CPR with 100 CPM in patients with non-traumatic out-of-hospital cardiac arrest. We randomly assigned patients with non-traumatic out-of-hospital cardiac arrest into two groups upon arrival to the emergency department (ED). The patients received manual CPR either with 100 CPM (CPR-100 group) or 120 CPM (CPR-120 group). The primary outcome measure was sustained restoration of spontaneous circulation (ROSC). The secondary outcome measures were survival discharge from the hospital, one-month survival, and one-month survival with good functional status. Of 470 patients with cardiac arrest, 136 patients in the CPR-100 group and 156 patients in the CPR-120 group were included in the final analysis. A total of 69 patients (50.7%) in the CPR-100 group and 67 patients (42.9%) in the CPR-120 group had ROSC (absolute difference, 7.8% points; 95% confidence interval [CI], -3.7 to 19.2%; P = 0.183). The rates of survival discharge from the hospital, one-month survival, and one-month survival with good functional status were not different between the two groups (16.9% vs. 12.8%, P = 0.325; 12.5% vs. 6.4%, P = 0.073; 5.9% vs. 2.6%, P = 0.154, respectively). We did not find differences in the resuscitation outcomes between those who received CPR with 100 CPM and those with 120 CPM. However, a large trial is warranted, with adequate power to confirm a statistically non-significant trend toward superiority of CPR with 100 CPM. ( CLINICAL TRIAL REGISTRATION INFORMATION: www.cris.nih.go.kr, cris.nih.go.kr number, KCT0000231).

Longitudinal Relationships Between Productive Activities and Functional Health in Later Years: A Multivariate Latent Growth Curve Modeling Approach.

This study examined the longitudinal relationships between functional health in later years and three types of productive activities: volunteering, full-time, and part-time work. Using the data from five waves (2000-2008) of the Health and Retirement Study, we applied multivariate latent growth curve modeling to examine the longitudinal relationships among individuals 50 or over. Functional health was measured by limitations in activities of daily living. Individuals who volunteered, worked either full time or part time exhibited a slower decline in functional health than nonparticipants. Significant associations were also found between initial functional health and longitudinal changes in productive activity participation. This study provides additional support for the benefits of productive activities later in life; engagement in volunteering and employment are indeed associated with better functional health in middle and old age.

Older Workers and Federal Work Programs: The Korean Senior Employment Program (KSEP).

Federal older worker programs are attracting attention due to the growing number of older workers across the world. They are uniquely situated to provide out-of-market work opportunities to older job seekers, who often find their age a barrier to securing desirable jobs. In 2004, the Korean government established its own program, the Korean Senior Employment Program (KSEP); however, literature for international readers on this innovative program is lacking. Thus, this article aims to provide an in-depth description of KSEP and a brief comparison between the Senior Community Service Employment Program in the U.S. and KSEP. The unique characteristics of KSEP include having the dual program foci on supplemental income and social participation; expanding work opportunities in the private sector beyond community-based jobs; accepting participants who are financially disadvantaged as well as those with a high desire for social participation regardless of their income; and broadening work opportunities for those with professional skills beyond repetitive, simple, and temporary jobs. This article may offer helpful insights to older worker advocates from various countries in creating or modifying their programs.

Addition of N-terminal pro-B-type natriuretic peptide levels to electrocardiography criteria for detection of left ventricular hypertrophy: the ARIRANG study.

The utility of electrocardiography (ECG) in screening for left ventricular hypertrophy (LVH) in general populations is limited mainly because its low sensitivity. B-type natriuretic peptide (BNP) is released due to the remodeling processes of LVH and could improve the diagnostic accuracy for the ECG criteria for LVH. We hypothesized that addition of BNP levels to ECG criteria could aid LVH detection compared with ECG alone in a general population. We enrolled consecutive 343 subjects from a community-based cohort. LVH was defined as LV mass index > 95 g/m(2) for females and > 115 g/m(2) for males according to echocardiography. The area under the receiver operator characteristic (ROC) curve to detect LVH was 0.55 (95% confidence interval [CI], 0.50-0.61) in Sokolow-Lyon criteria and 0.53 (0.47-0.59) in the Cornell voltage criteria. After addition of N-terminal-proBNP levels to the model, the corresponding areas under the ROC were 0.63 (0.58-0.69) and 0.64 (0.59-0.69), respectively. P values for the comparison in areas under the ROC for models with and without N-terminal-proBNP levels were < 0.001. These data suggest that addition of N-terminal-proBNP levels to ECG criteria could significantly improve the diagnostic accuracy of LVH in general populations.